1. Field of the Invention
The invention relates to pharmaceutical formulations of thioctic acid and the enantiomers thereof. Formulations according to the invention are used for the production of pharmaceutical dosage forms which release the active ingredient more rapidly and have greater bioavailability than previous dosage forms.
2. Description of the Related Art
Thioctic acid (.alpha.-lipoic acid) is chemically 1,2-dithia-cyclopentane-3-valeric acid. The production of free R-thioctic acid is described, for example, in DE-OS 41 37 773.
Thioctic acid is a component of cell metabolism and is thus found in many plants and animals. It acts as one of the coenzymes during oxidative decarboxylation of pyruvate and other .alpha.-keto acids. Thioctic acid has been used for some time in various conditions, for example, inter alia, in liver conditions, in liver damage due to fungal poisoning and in diabetic and alcoholic polyneuropathy, a degeneration of the peripheral nerves which accompanies metabolic disorders.
The present invention relates to pharmaceutical formulations containing thioctic acid or solid salts of thioctic acid with improved bioavailability.
This invention relates not only to the racemic form, but also to the pure (R)- or (S)-thioctic acid as well as to mixtures of (R)- and (S)-thioctic acid of any desired composition. Of the pure optical isomers of thioctic acid (R- and S-form, ie. R-thioctic acid and S-thioctic acid), unlike the racemate, the R-enantiomer has a predominantly anti-inflammatory action and the S-enantiomer has a predominantly anti-nociceptive action, wherein the anti-inflammatory action of the R-enantiomer is, for example, stronger than that of the racemate by a factor of 10.
The anti-nociceptive (analgesic) action of the S-enantiomer is, for example, stronger than that of the racemate by a factor of 6.
Thus, in comparison with the racemate, the enantiomers are much more specific and effective active ingredients.
The actions are described in EP 427 246 and EP 427 247 and in GbM 90 17 987.0 and EP 530 446.
A combination of thioctic acid with vitamins is described in EP 572 922.
R,S-Thioctic acid has a melting point of 60.5.degree. C. R-Thioctic acid has a melting point of 50.6-50.7.degree. C. Both are soluble at 25.degree. C. in water at a rate of 12.14 mg/10 ml and in methanol, ethanol, chloroform, dimethylformamide and n-octanol at a rate of above 1000 mg/10 ml.
In comparison with parenteral dosage forms, orally administrable pharmaceutical preparations have a price advantage, which has a favourable effect on daily therapeutic costs. However, previous dosage forms of thioctic acid have the disadvantage of having relatively low bioavailability. Low bioavailability means that, on oral administration of the dosage form, in comparison with intravenous administration, relatively little of the unaltered active ingredient is found in the blood of the test subject or patient. As a consequence, oral administration of the medication cannot be as effective as intravenous administration of the active ingredient. There is thus an object of developing dosage forms which, together with good storage stability, have the greatest possible bioavailability.